Department of Chemistry, Faculty of Pharmacy, Medical University-Sofia, 1000 Sofia, Bulgaria.
Department of Physics and Biophysics, Faculty of Medicine, Medical University-Sofia, 1431 Sofia, Bulgaria.
Int J Mol Sci. 2020 Nov 23;21(22):8862. doi: 10.3390/ijms21228862.
Increased levels of the superoxide radical are associated with oxidative damage to healthy tissues and with elimination of malignant cells in a living body. It is desirable that a chemotherapeutic combines pro-oxidant behavior around and inside tumors with antioxidant action near healthy cells. A complex consisting of a pro-oxidant cation and antioxidant ligands could be a potential anticancer agent. Ga(III) salts are known anticancer substances, and 5-aminoorotic acid (HAOA) is a ligand with antioxidant properties. The in vitro effects of HAOA and its complex with Ga(III) (gallium(III) 5-aminoorotate (GaAOA)) on the in vitro accumulation of superoxide and other free radicals were estimated. Model systems such as potassium superoxide (KO), xanthine/xanthine oxidase (X/XO), and rat blood serum were utilized. Data suggested better antioxidant effect of GaAOA compared to HAOA. Evidently, all three ligands of GaAOA participated in the scavenging of superoxide. The effects in rat blood serum were more nuanced, considering the chemical and biochemical complexity of this model system. It was observed that the free-radical-scavenging action of both compounds investigated may be manifested via both hydrogen donation and electron transfer pathways. It was proposed that the radical-scavenging activities (RSAs) of HAOA and its complex with Ga(III) may be due to a complex process, depending on the concentration, and on the environment, nature, and size of the free radical. The electron transfer pathway was considered as more probable in comparison to hydrogen donation in the scavenging of superoxide by 5-aminoorotic acid and its gallium(III) complex.
超氧自由基水平的增加与健康组织的氧化损伤以及活体中恶性细胞的消除有关。理想情况下，化疗药物应在肿瘤周围和内部具有促氧化剂行为，并在健康细胞附近具有抗氧化作用。由促氧化剂阳离子和抗氧化配体组成的配合物可能是一种潜在的抗癌剂。Ga（III）盐是已知的抗癌物质，5-氨基乳清酸（HAOA）是一种具有抗氧化性质的配体。本文研究了 HAOA 及其与 Ga（III）（三价镓 5-氨基乳清酸盐（GaAOA））形成的配合物对超氧自由基和其他自由基在体外积累的影响。利用了钾超氧化物（KO）、黄嘌呤/黄嘌呤氧化酶（X/XO）和大鼠血清等模型系统。结果表明，与 HAOA 相比，GaAOA 具有更好的抗氧化作用。显然，GaAOA 的三种配体都参与了超氧自由基的清除。考虑到该模型系统的化学和生化复杂性，大鼠血清中的作用更为复杂。观察到，所研究的两种化合物的自由基清除作用可能通过氢供体和电子转移两种途径表现出来。研究提出，HAOA 及其与 Ga（III）的配合物的自由基清除活性（RSA）可能是一个复杂的过程，取决于浓度以及自由基的环境、性质和大小。与氢供体相比，电子转移途径更有可能是 5-氨基乳清酸及其镓（III）配合物清除超氧自由基的途径。
